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. 2024 Jan 19;10(3):eadg1222. doi: 10.1126/sciadv.adg1222

Fig. 8. Modeling AF in iPSC-aCMs with E428K mutation in SCN5A.

Fig. 8.

(A) Left to right: Schematics of family tree with E428K mutation and an unaffected genetic control (wild type), isolation of peripheral blood mononuclear cells (PBMCs), generation of iPSCs from PBMCs, and CRISPR correction to generate a genome-corrected (GC) control. Diagram constructed in BioRender. (B) OVM traces comparing PC to RM for the iPSC lines showed a uniform beating pattern in the control line and an irregular beating pattern in the E428K line, which was corrected with the E248K-GC line. (C) An increase in beats per minute was observed in the E428K line versus control and GC lines; however, values were higher in RM versus PC, which was closer to the adult heart’s beating rates (n = 8 cells). (D) An increase in coefficient of variation (mean peak-to-peak interval divided by the SD) was observed in the E428K line compared to the control and GC lines in both RM and PC (n = 8 cells for control and E428K-GC lines; n = 11 cells for RM E428K line; n = 14 cells for PC E428K line). (E) Coefficient of variation was significantly decreased in E428K-PC treated with both 1 and 10 μM ranolazine (Rano), whereas a significant decrease was observed only at 10 μM Rano treatment in E428K-RM, suggesting that PC are more sensitive to Rano treatment (n = 11 cells). *P < 0.05, **P < 0.01, and ****P < 0.0001.